The COVID-19 pandemic, an environmental neurology perspective.

Neurologists have a particular interest in SARS-CoV-2 because the nervous system is a major participant in COVID-19, both in its acute phase and in its persistent post-COVID phase. The global spread of SARS-CoV-2 infection has revealed most of the challenges and risk factors that humanity will face in the future. We review from an environmental neurology perspective some characteristics that have underpinned the pandemic. We consider the agent, SARS-CoV-2, the spread of SARS-CoV-2 as influenced by environmental factors, its impact on the brain and some containment measures on brain health. Several questions remain, including the differential clinical impact of variants, the impact of SARS-CoV-2 on sleep and wakefulness, and the neurological components of Long-COVID syndrome. We touch on the role of national leaders and public health policies that have underpinned management of the COVID-19 pandemic. Increased awareness, anticipation and preparedness are needed to address comparable future challenges.

Nodding syndrome: A key role for sources of nutrition?

Nodding Syndrome (NS) has occurred among severely food-stressed communities in northern Uganda and several other East African populations that, with their forced physical displacement, have resorted to nutritional support from available wild plants and fungi, some of which have neurotoxic potential. Among the latter is an agaric mushroom with an unknown content of hydrazine-generating agaritine, namely Agaricus bingensis, the unusually wide consumption of which may relate to the low serum levels of vitamin B6 in Ugandan NS subjects relative to controls. Hydrazine-related compounds induce patterns of DNA damage that promote neuropathological changes (tauopathy) reminiscent of those associated with established NS. While the cause of this childhood brain disease is unknown, we encourage increased attention to the role of malnutrition and B6 hypovitaminosis in the etiology of this devastating brain disease.

An amyotrophic lateral sclerosis hot spot in the French Alps associated with genotoxic fungi.

Between 1990 and 2018, 14 cases of amyotrophic lateral sclerosis (ALS) were diagnosed in residents of, and in visitors with second homes to, a mountainous hamlet in the French Alps. Systematic investigation revealed a socio-professional network that connected ALS cases. Genetic risk factors for ALS were excluded. Several known environmental factors were scrutinized and eliminated, notably lead and other chemical contaminants in soil, water or home-grown vegetation used for food, radon and electromagnetic fields. Some lifestyle-related behavioral risk factors were identified: Prior to clinical onset of motor neuron disease, some patients had a high degree of athleticism and smoked tobacco. Recent investigations on site, based on a new hypothesis, showed that all patients had ingested wild mushrooms, notably poisonous False Morels. Half of the ALS cohort reported acute illness following Gyromitra gigas mushroom consumption. This finding supports the hypothesis that genotoxins of fungal origin may induce motor neuron degeneration.

Environmental neurology in the tropics.

We address the impact of the tropical environment on the human nervous system using the multifaceted approach characteristic of environmental neurology. First, environmental factors are examined according to their nature (physical, chemical and biological) and in relation to human activity and behavior. Some factors are specific to the tropics (climate and infections), while others are non-specific (chemicals, human communities and their way of life). Second, we examine the major role of human adaptation to the success of Homo sapiens, with emphasis on the linkage between thermoregulation and sleep-wake regulation. Third, we examine the performance of environmental neurology as a clinical discipline in tropical climates, with focus on the diagnostic and therapeutic challenges posed by human African trypanosomiasis. Finally, the prevention, early detection and monitoring of environmental neurological diseases is examined, as well as links with political and economic factors. In conclusion, practitioners of environmental neurology seek a global, multidisciplinary and holistic approach to understanding, preventing and treating neurological disorders within their purview. Environmental neurology integrates an expanded One Health concept by linking health and wellness to the interaction of plants, animals, humans and the ecosystem. Recent epidemics and the current COVID-19 pandemic exemplify the need for worldwide action to protect human health and biodiversity.

Jean Rodier: History of Manganism in Morocco.

Jean Rodier (1920-2003), distinguished researcher and scientist, directed the Toxicology Department of Hygiene Institute of Rabat under the French Protectorate. From 1946, he developed numerous lines of research in occupational health, in particular on Manganism, a neurological disorder that impacted miners in his home country of Morocco. His many papers on Manganism, only one of which was published in English, describe field and laboratory research studies that focused its prevention and management.

Nodding syndrome phenotypes.

Nodding syndrome (NS) is a progressive encephalopathy of children and adolescents characterized by seizures, including periodic vertical head nodding. Epidemic NS, which has affected parts of East Africa, appears to have clinical overlap with sub-Saharan Nakalanga syndrome (NLS), a brain disorder associated with pituitary dwarfism that appears to have a patchy distribution across sub-Sahara. Clinical stages of NS include inattention and blank stares, vertical head nodding, convulsive seizures, multiple impairments, and severe cognitive and motorsystem disability, including features suggesting parkinsonism. Head nodding episodes occur in clusters with an electrographic correlate of diffuse high-amplitude slow waves followed by an electrodecremental pattern with superimposed diffuse fast activity. Brain imaging reveals differing degrees of cerebral cortical and cerebellar atrophy. Brains of NS-affected children with mild frontotemporal cortical atrophy display neurofibrillary pathology and dystrophic neurites immunopositive for tau, consistent with a progressive neurodegenerative disorder. The etiology of NS and NLS appears to be dominated by environmental factors, including malnutrition, displacement, and nematode infection, but the specific cause is unknown.

Medical management, prevention and mitigation of environmental risks factors in Neurology.

The human environment and exposures arising therefrom are major contributors to neurological disorders ranging from stroke to neurodegenerative diseases. Reduction of exposure to environmental risk factors, with the goal of disease prevention or control, is addressed at the individual as well as the societal level and in recognition of differential subject vulnerability. We examine some practical solutions in high-income countries that may allow a better adaptation to environmental risks and reduce their adverse impact on the nervous system. We consider the citizen's role in reducing unhealthy exposures and explore new approaches to treatment.

Plants with neurotoxic potential in undernourished subjects.

The consumption by humans of plants with potential to induce neurological disorders is widespread, but overt disease surfaces only when the subject's toxic threshold is exceeded. Excessive intake arising from food dependency in the setting of hunger, chronic undernutrition, vitamin deficiency, inadequate detoxication, or other individual susceptibility, can trigger acute encephalopathy (lychee, ackee fruits), sub-acute spastic paraparesis (grasspea, cassava root/leaves) or ataxic neuropathy (cassava root flour). While these disorders are very rarely encountered in high-income countries, they are not only common among impoverished populations but also often occur as outbreaks that impact a significant proportion of an affected community. Unfamiliarity with the adverse effects of plant toxins has sometimes led to the mistaken attribution of nutritional neurotoxic disease to a neurotropic viral or synthetic pesticidal etiology. The combination of human population growth, food and water insecurity, poverty and, with climate change, increased dependency on environmentally tolerant plants with neurotoxic potential, predictably may result in an increased prevalence of nutritional neurotoxic disorders, especially in certain parts of Africa and Asia.

ALS and environment: Clues from spatial clustering?

A role for environmental factors in the etiology of amyotrophic lateral sclerocis (ALS) has been suspected for many years. A large body of work has implicated common exposures, conjugal cases, at-risk activities, heavy metals, organic solvents, and electric shocks, among others. One of the most demonstrative relationships between ALS and the environment is spatial clustering. We reviewed the most important and recent spatial clusters in a given area, whatever the geographical size, with either substantial epidemiological approaches or with highly significant associations, and with precise hypotheses. We present a broad, albeit incomplete overview of investigations in different areas, including examples of the difficulties and contradictions of some approaches. Most of the time, the implication of neurotoxins is suspected and, although not always strictly identified, some candidates are emerging: cycasin, MAM, L-BMAA, hydrazine, for example. One other important point is the possibility of interaction among risk/causal factors that increase the complexity of investigation. Additionally, with the exception of Western Pacific ALS, studies of spatial clustering are lacking a major methodological approach, namely a large cohort analysis extended over a long period of time, and probably for decades. Nevertheless, any spatial cluster needs to be identified, described and studied as deeply as possible to illuminate knowledge of the origin of this devastating disorder and to promote primary or secondary disease prevention.

Parkinson's disease and solvents: Is there a causal link?

We report here on chronic neurological impairment in three car painters with constant occupational exposure to organic solvents. All had a clinical presentation of Parkinson's disease and, in all cases, SPECT DaTscan brain imaging, using 123I-FP-CIT, showed bilateral reduction of tracer uptake in the basal ganglia, evidence of dysfunction at the dopaminergic terminal.

Azañón's disease. A 19th century epidemic of neurolathyrism in Spain.

The cultivation and consumption of grasspea (Lathyrus sativus) in Spain probably dates back centuries, especially during times of famine when the neurotoxic potential of this legume was expressed in the form of a spastic paraparesis known as neurolathyrism. Little known outside the country, the epidemic of neurolathyrism in the years following the Spanish Civil War (1936-1939) came to affect more than a thousand people. In late 1872, during the Six Years Revolutionary Term, young Alejandro San Martín Satrústegui (1847-1908), then editor of the popular weekly El Siglo Médico, travelled to Azañón, a remote village in the province of Guadalajara, to clarify a so-far unknown disease. We analysed the original article published in 1873 by San Martin, as well as communications sent by El Siglo Médico readers reporting similar cases in many other Castilian provinces. San Martín's neurological findings in seven personally examined cases were astonishingly accurate; he concluded the subjects' neurological deficits resulted from injury to the lateral columns in the lower portion of the spinal cord. Description of the clinical findings provided both by San Martín, and by the readers of El Siglo Médico, leave no doubt as to the diagnosis of neurolathyrism. However, none suspected the patient's staple food was the determinant cause of the disease. San Martín proposed the eponym Azañón's disease for lack of a better name the same year (1873) in which Cantani in Italy introduced the term lathyrism. The epidemic of neurolathyrism that affected many Castilian towns represents one of the best-documented in Europe during the last third of the 19th century.

Nodding syndrome: 2015 International Conference Report and Gulu Accord.

Nodding syndrome is a pediatric epileptic encephalopathy of apparent environmental origin that was first described in Tanzania, with recent epidemics in South Sudan and Uganda. Following a brief description of the medical geography, setting and case definition of this progressive brain disorder, we report recent advances relating to etiology, diagnosis and treatment described in papers given at the 2nd International Conference on Nodding Syndrome held in July 2015 in Gulu, Uganda. The target audience for this report includes: anthropologists, entomologists, epileptologists, health care workers, helminthologists, medical researchers, neuroepidemiologists, neurologists, neuroscientists, neuropathologists, nurses, nutritional scientists, primary health care physicians, psychiatrists, public health practitioners, toxicologists, and virologists.

Nodding syndrome: origins and natural history of a longstanding epileptic disorder in sub-Saharan Africa.

BACKGROUND: Repetitive involuntary head nodding was first reported in the 1960s in the Wapogoro tribe of Tanzania. OBJECTIVES: We describe the natural history of head nodding in the Wapogoro tribe, with special reference to the earliest reported dates of onset. METHODS: We analyzed clinical data from 150 historical patients seen between 1960 and 1971. RESULTS: Head nodding with or without grand mal convulsions was present in 33/150 (∼20%) cases, was mostly familial and equally distributed by gender. Age at onset of head nodding ranged from 2-22 years (mean: ∼10 years) in the period 1934-1962. Head nodding preceded onset of grand mal convulsions by up to 12 months, and motor and psychomotor deficits indicative of brain damage developed with time. Fourteen of the 33 cases died at 13-39 years of age (mean: ∼20 years) while nineteen aged 16-28 years (mean: ∼16 years) were still alive. CONCLUSION: Historical accounts of head nodding (amesinzia kichwa, Swahili) among the Wapogoro tribe fit the August 2012 World Health Organization (WHO) case definition of probable Nodding Syndrome. Reported to have existed in this population for at least 80 years, Nodding Syndrome is a progressive seizure disorder that leads to generalized convulsions (kifafa), brain damage and death.

Nodding syndrome in Mundri county, South Sudan: environmental, nutritional and infectious factors.

BACKGROUND: Nodding Syndrome is a seizure disorder of children in Mundri County, Western Equatoria, South Sudan. The disorder is reported to be spreading in South Sudan and northern Uganda. OBJECTIVE: To describe environmental, nutritional, infectious, and other factors that existed before and during the de novo 1991 appearance and subsequent increase in cases through 2001. METHODS: Household surveys, informant interviews, and case-control studies conducted in Lui town and Amadi village in 2001-2002 were supplemented in 2012 by informant interviews in Lui and Juba, South Sudan. RESULTS: Nodding Syndrome was associated with Onchocerca volvulus and Mansonella perstans infections, with food use of a variety of sorghum (serena) introduced as part of an emergency relief program, and was inversely associated with a history of measles infection. There was no evidence to suggest exposure to a manmade neurotoxic pollutant or chemical agent, other than chemically dressed seed intended for planting but used for food. Food use of cyanogenic plants was documented, and exposure to fungal contaminants could not be excluded. CONCLUSION: Nodding Syndrome in South Sudan has an unknown etiology. Further research is recommended on the association of Nodding Syndrome with onchocerciasis/mansonelliasis and neurotoxins in plant materials used for food.

Clinical and epidemiologic characteristics of nodding syndrome in Mundri County, southern Sudan.

BACKGROUND: Nodding syndrome (repetitive nodding and progressive generalized seizures) is assuming epidemic proportions in South Sudan, Tanzania and Uganda. OBJECTIVE: To describe clinical and epidemiological features of nodding syndrome in southern Sudan based on preliminary investigations conducted in 2001 and 2002. METHOD: Household surveys, clinical, electrophysiological (EEG) assessments, informant interviews and case-control studies were conducted in the town of Lui and the village of Amadi in southern Sudan. RESULTS: Nodding syndrome is characterized by involuntary repetitive nodding of the head, progressing to generalized seizures; mental and physical deterioration. The EEGs were consistent with progressive epileptic encephalopathy. Prevalence of Nodding syndrome in Lui and Amadi was 2.3% and 6.7% respectively. All case control studies showed a positive association between cases and Onchocerca volvulus. A history of measles was negatively associated with being a case: 2/13 of cases and 11/19 of controls had had measles: odds ratio 0.13 (95% CI 0.02, 0.76). Environmental assessment did not reveal any naturally occurring or manmade neurotoxic factors to explain Nodding Syndrome, although fungal contamination of food could not be ruled out. CONCLUSION: Nodding Syndrome was strongly associated with Onchocerca volvulus. There was no evidence to suggest an environmental pollutant, chemical agent, or other toxic factor.